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Integr Mol Med. 2019 Aug;6(4). doi: 10.15761/IMM.1000375. Epub 2019 Jul 15.

Unlimited expansion of intestinal stem cells from a wide range of ages.

Author information

1
Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.
2
Tract Pharmaceuticals, Inc., Marlborough, Massachusetts 01752, USA.
3
Division of Gastroenterology, Baylor College of Medicine, Houston, Texas, USA.
4
Department of Pediatrics, Division of Gastroenterology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
5
Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's, Medical Center, Hartford, Connecticut 06106, USA.
6
Departments of Medicine and Pathology, National University of Singapore, Singapore.
7
Institute of Molecular Medicine, McGovern Medical School of The University of Texas, Health Science Center, Houston, Texas 77030, USA.
8
Department of Biochemistry and Molecular Biology, University of Texas McGovern, Medical School, Houston, Texas 77030, USA.

Abstract

The recent technical advance in cloning and culturing ground-state intestinal stem cells (ISC) provides us an opportunity of accurate assessment of age-related impact on the function of highly proliferative intestinal stem cells. Our ability of indefinitely and robustly expanding single-stem-cell derived pedigrees in vitro allows us to study intestinal stem cells at the clonal level. Interestingly, comparable number of ISC clones was yielded from 1mm endoscopic biopsy of all donors despite the age. They were passaged in vitro as pedigrees and expanded to 1 billion cells in approximately sixty days without changes in stemness demonstrated by clonogenicity and multipotency. Therefore, our study shows that ISCs from a wide range of ages can be cloned and expanded to unlimited number in vitro with similar efficiency and stability. These patient-derived ISCs harbor intrinsic immortality and are ideal for autologous transplantation, supporting the promise of adult-stem-cell based personalized medicine.

Conflict of interest statement

Conflicts of interest statement W.X., F.M., M.D. and M.V have filed a patent related to the technology used in the present work and Drs. Xian and McKeon have financial interests in MultiClonal Therapeutics Inc.

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